Magnetic bead actuation using feedback for FTIR biosensor

Abstract

A method for controlling actuation of label particles in a biosensor device, e.g., using frustrated total internal reflection, includes applying a predetermined actuation force on the label particles and determining the effect of the applied actuation force in a binding volume or surface of a sensor cartridge of the biosensor device. A feedback control of the actuation force is applied.

The invention claimed is: 
     
       1. A method for controlling actuation of label particles in a biosensor device having a sensor chamber including a binding surface for binding the label particles, the method comprising:
 applying a magnetic field to the sensor chamber to generate a predtermined actuation force for actuating the label particles; 
 determining an effect of the actuation force in the binding surface by projecting a light onto the binding surface and imaging a reflection of the light; and 
 controlling the actuation force based on the determined effect in the binding surface, 
 wherein determining the effect of the actuation force in the binding surface includes interpreting when a slope of a plot of light intensity reflected from the binding surface versus the applied magnetic field is no longer substantially constant. 
 
     
     
       2. The method according to  claim 1 , wherein the actuation force is controlled by controlling a current in actuation coils generating the magnetic actuation force. 
     
     
       3. The method according to  claim 1 , wherein the actuation force is controlled by controlling a position of actuation coils generating the magnetic actuation force with respect to the sensor chamber. 
     
     
       4. The method according to  claim 1 , wherein determining the effect of the applied actuation force includes observing the binding surface. 
     
     
       5. The method according to  claim 4 , wherein the binding surface is observed by detecting light scattered from the surface. 
     
     
       6. The method according to  claim 1 , wherein the biosensor device includes a frustrated total internal reflection magnetic biosensor device. 
     
     
       7. The method according to  claim 1 , further comprising determining the effect of the actuation force in non-binding area of the sensor chamber. 
     
     
       8. The method according to  claim 7 , further comprising simultaneously observing in real-time the effect of the actuation force in the binding surface and the effect of the applied actuation force in non-binding areas of the sensor chamber. 
     
     
       9. The method according to  claim 1 , wherein the controlling act controls the actuation force to remove only non-bonded beads from the binding surface based on real-time observation of the binding surface for determining the effect of the actuation force in the binding surface. 
     
     
       10. The method according to  claim 1 , further comprising determining a quality of the binding of the label particles to the binding surface by increasing a force directed away from the binding surface until bonded label particles disappear from the binding surface. 
     
     
       11. A method for controlling actuation of label particles in a Frustrated Total Internal Reflection (FTIR) biosensor device, comprising:
 applying a magnetic field to a sensor cartridge to generate an actuation force for actuating a plurality of label particles; 
 observing an effect of the actuation force in a binding volume or surface of the sensor cartridge including projecting a light onto the binding volume or surface and image a reflection of the light from the blinding volume of surface; 
 analyzing an intensity of the reflected light to identify a threshold value (H thres ) for the magnetic field, wherein the analyzing includes determining when the intensity of the reflected light versus the magnetic field becomes no longer substantially constant; and 
 controlling the magnetic field so that it is below the identified H thres . 
 
     
     
       12. The method to  claim 11  wherein the H thres identifies the strength of the magnetic field which is required to remove substantially all label particles which are not bond to the binding volume or surface of the sensor cartridge without removing label particles which are bond to the binding volume or surface. 
     
     
       13. The method according to  claim 11 , wherein the observing and analyzing steps are both performed in real-time.